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Nivolumab and Brentuximab Vedotin in Treating Older Patients With Untreated Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2017 by Academic and Community Cancer Research United
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Academic and Community Cancer Research United
ClinicalTrials.gov Identifier:
NCT02758717
First received: April 12, 2016
Last updated: April 5, 2017
Last verified: February 2017
  Purpose
This phase II trial studies how well nivolumab and brentuximab vedotin work in treating older patients with untreated Hodgkin lymphoma. Monoclonal antibodies, such as nivolumab, may block cancer growth in different ways by targeting certain cells. Biological therapies, such as brentuximab vedotin, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Nivolumab and brentuximab vedotin may work better in treating older patients with untreated Hodgkin lymphoma.

Condition Intervention Phase
Classical Hodgkin Lymphoma
Stage IB Hodgkin Lymphoma
Stage II Hodgkin Lymphoma
Stage IIA Hodgkin Lymphoma
Stage IIB Hodgkin Lymphoma
Stage III Hodgkin Lymphoma
Stage IIIA Hodgkin Lymphoma
Stage IIIB Hodgkin Lymphoma
Stage IV Hodgkin Lymphoma
Stage IVA Hodgkin Lymphoma
Stage IVB Hodgkin Lymphoma
Drug: Brentuximab Vedotin
Other: Laboratory Biomarker Analysis
Biological: Nivolumab
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase II, Multi-center Trial of Nivolumab and Brentuximab Vedotin in Patients With Untreated Hodgkin Lymphoma Over the Age of 60 Years or Unable to Receive Standard Adriamycin, Bleomycin, Vinblastine, and Dacarbazine (ABVD) Chemotherapy

Resource links provided by NLM:


Further study details as provided by Academic and Community Cancer Research United:

Primary Outcome Measures:
  • Rate of complete metabolic response [ Time Frame: 18 weeks ]
    The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.


Secondary Outcome Measures:
  • Duration of response [ Time Frame: From date at which the patient's objective status is first noted to be a CMR or PMR to the earliest date progression (PMD or PD) is documented, assessed up to 7 years ]
    The distribution of duration of response will be estimated using the method of Kaplan-Meier.

  • Incidence of adverse events graded by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 7 years ]
    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

  • Overall response rate estimated by the total number of complete and partial metabolic responses (CMR or PMR) divided by the total number of evaluable patients [ Time Frame: Up to 7 years ]
    Exact binomial 95% confidence intervals for the true overall response rate will be calculated.

  • Overall survival [ Time Frame: Time from registration to death due to any cause, assessed up to 7 years ]
    The distribution of overall survival will be estimated using the method of Kaplan-Meier.

  • Progression-free survival [ Time Frame: Time from registration to the earliest date of documentation of disease progression (PMD or PD) or death due to any cause, assessed up to 7 years ]
    The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.


Other Outcome Measures:
  • Change in genetic variability [ Time Frame: Day 1 to up to 7 years ]
    Baseline values and changes in these parameters over time will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (paired t-tests Wilcoxon signed rank tests and Fisher's exact tests for interval, ordinal and nominal level data, respectively) will be used to assess changes in these variables before and after therapy. In addition, baseline values and changes over time in each measure will be explored in relation to clinical outcome to explore any differences between responders and non-responders and by depth of response (CMR vs. PMR) to iden

  • Change in intratumoral cell populations [ Time Frame: Day 1 to up to 7 years ]
    Baseline values and changes in these parameters over time will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (paired t-tests Wilcoxon signed rank tests and Fisher's exact tests for interval, ordinal and nominal level data, respectively) will be used to assess changes in these variables before and after therapy. In addition, baseline values and changes over time in each measure will be explored in relation to clinical outcome to explore any differences between responders and non-responders and by depth of response (CMR vs. PMR) to iden

  • Change in serum cytokines [ Time Frame: Day 1 to up to 7 years ]
    Baseline values and changes in these parameters over time will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (paired t-tests Wilcoxon signed rank tests and Fisher's exact tests for interval, ordinal and nominal level data, respectively) will be used to assess changes in these variables before and after therapy. In addition, baseline values and changes over time in each measure will be explored in relation to clinical outcome to explore any differences between responders and non-responders and by depth of response (CMR vs. PMR) to iden

  • Change in T cell activation [ Time Frame: Day 1 to up to 7 years ]
    Baseline values and changes in these parameters over time will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (paired t-tests Wilcoxon signed rank tests and Fisher's exact tests for interval, ordinal and nominal level data, respectively) will be used to assess changes in these variables before and after therapy. In addition, baseline values and changes over time in each measure will be explored in relation to clinical outcome to explore any differences between responders and non-responders and by depth of response (CMR vs. PMR) to iden


Estimated Enrollment: 75
Study Start Date: May 2016
Estimated Study Completion Date: May 2024
Estimated Primary Completion Date: November 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (brentuximab vedotin, nivolumab)
Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for 7 courses and 6-8 weeks in course 8 in the absence of disease progression or unacceptable toxicity.
Drug: Brentuximab Vedotin
Given IV
Other Names:
  • ADC SGN-35
  • Adcetris
  • Anti-CD30 Antibody-Drug Conjugate SGN-35
  • Anti-CD30 Monoclonal Antibody-MMAE SGN-35
  • Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35
  • cAC10-vcMMAE
  • SGN-35
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the efficacy based on complete metabolic remission (CMR) rate of brentuximab vedotin/nivolumab in previously untreated Hodgkin lymphoma patients 60 years of age or older, or those considered unsuitable for standard chemotherapy because of a low cardiac ejection fraction (< 50%) or impaired pulmonary or renal function.

SECONDARY OBJECTIVES:

I. The overall response rate (CMR + partial metabolic response [PMR]). II. Safety and tolerability of the regimen in this patient population. III. Duration of response (DOR). IV. Progression-free survival (PFS). V. Overall survival (OS).

TERTIARY OBJECTIVES:

I. T-cell/cytokine - peripheral blood specimens will be used to assess T-cell activation and cytokine up regulation as measures of treatment effect.

II. Biomarkers - intratumoral cell populations, genetic variability, serum cytokines and T-cell activation will be evaluated to identify potential biomarkers that correlate with response to therapy.

OUTLINE:

Patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for 7 courses and 6-8 weeks in course 8 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30, 60, 90, 150, 210, 270 days, every 90 days for 2 years, and then every 6 months for 5 years.

  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Classical Hodgkin lymphoma determined by local hematopathology review
  • One of the following:

    • Age >= 60 years
    • Patients =< 60 years that are unsuitable for, or refused, standard chemotherapy because of a cardiac ejection fraction of < 50%, a pulmonary diffusion capacity < 80%, or a creatinine clearance < 30 mL/min
  • Requirement for systemic chemotherapy: all stages except IA (not bulky disease), if involved field is considered radiotherapy (RT) curative
  • Previously untreated with either chemotherapy, radiation therapy or either brentuximab vedotin or nivolumab, or another check point inhibitor
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Leukocytes >= 3,000/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin > 9.0 g/dL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate transaminase (AST) =< 2.5 x ULN
  • Alanine transaminase (ALT) =< 2.5 x ULN
  • Creatinine =< 2.0 mg/dL
  • Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to registration; Note: women of child-bearing potential (WOCBP) must use appropriate method(s) of contraception; WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug; men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product; women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study); Note: During the Active Monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
  • Ability to understand and willingness to sign an informed written consent
  • Provide blood and tissue samples for mandatory correlative research purposes

Exclusion Criteria:

  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Active, known or suspected autoimmune disease; Note: Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
  • Use of systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications =< 14 days of registration; Note: Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • Immunocompromised patients, patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) and currently receiving antiretroviral therapy, patients with a prior history of known or suspected autoimmune disease, active Hepatitis B virus surface antigen (HBV sAg+), active Hepatitis C (if antibody [Ab]+ then polymerase chain reaction [PCR]+) indicating acute or chronic infection, a history of pancreatitis and/or interstitial lung disease
  • Allergy to brentuximab vedotin and/or nivolumab
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Have had prior chemotherapy or radiotherapy for Hodgkin lymphoma
  • Have received either of the study drugs
  • < 60 years who are considered candidates for standard chemotherapy
  • >= grade 2 peripheral neuropathy
  • Other active malignancy =< 2 years prior to registration, unless treated with curative intent; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer
  • Active central nervous system (CNS) involvement or leptomeningeal metastases involvement
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02758717

Locations
United States, California
Stanford Cancer Institute Recruiting
Palo Alto, California, United States, 94304
Contact: Ranjana H. Advani       radvani@stanford.edu   
Principal Investigator: Ranjana H. Advani         
United States, District of Columbia
MedStar Georgetown University Hospital Recruiting
Washington, District of Columbia, United States, 20007
Contact: Bruce D. Cheson    507-266-0800    bdc4@georgetown.edu   
Principal Investigator: Bruce D. Cheson         
United States, Illinois
University of Chicago Comprehensive Cancer Center Withdrawn
Chicago, Illinois, United States, 60637
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Stephen M. Ansell       Ansell.stephen@mayo.edu   
Principal Investigator: Stephen M. Ansell         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Nancy L. Bartlett       nbartlet@wustl.edu   
Principal Investigator: Nancy L. Bartlett         
United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Kristie A. Blum       Kristie.blum@osumc.edu   
Principal Investigator: Kristie A. Blum         
United States, Texas
M D Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Michelle A. Fanale       mfanale@mdanderson.org   
Principal Investigator: Michelle A. Fanale         
Sponsors and Collaborators
Academic and Community Cancer Research United
National Cancer Institute (NCI)
Investigators
Principal Investigator: Bruce Cheson Academic and Community Cancer Research United
  More Information

Responsible Party: Academic and Community Cancer Research United
ClinicalTrials.gov Identifier: NCT02758717     History of Changes
Other Study ID Numbers: RU051505I
NCI-2016-00468 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RU051505I ( Other Identifier: Academic and Community Cancer Research United )
P30CA015083 ( US NIH Grant/Contract Award Number )
Study First Received: April 12, 2016
Last Updated: April 5, 2017

Additional relevant MeSH terms:
Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Antibodies
Immunoglobulins
Immunoconjugates
Nivolumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 25, 2017